Wu Yun, Shi Huixin, Li Wei, An Yijun, Shao Yuhan, Rao Xia, Waterfield Nicholas R, Wang Wei, Yang Guowei
Beijing Institute of Tropical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Warwick Medical School, Warwick University, Coventry, UK.
Infect Drug Resist. 2024 Dec 17;17:5619-5627. doi: 10.2147/IDR.S491478. eCollection 2024.
pneumonia (PJP) shows a high fatality rate in non-HIV patients. However, there are limited data on drug resistance-related gene mutations in these patients. This study aimed to describe the prevalence of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of in non-HIV patients in China, providing a reference for drug usage.
We analyzed the polymorphisms of DHPS and DHFR genes from 45 non-HIV patients in China, including infection (n = 14) and colonization (n = 31). This analysis also considered clinical characteristics, burden, treatment response, and prognosis.
Compared to the colonization, infection had significantly altered blood indicators (GR%, LY%, HGB, TP, ALB, CRP, <0.05) with higher burden (<0.05) and worse prognosis (<0.05). Additionally, patients with infection were more susceptible to infections, such as the Epstein-Barr virus, Cytomegalovirus, Mycoplasma and Klebsiella pneumoniae. Although no known drug-resistance mutations were detected in the DHPS gene in this study, 10 nonsynonymous mutations were identified. Furthermore, 10 nonsynonymous and 2 synonymous mutations were found in the DHFR gene. However, these mutations were not associated with a worse prognosis.
Our results implied that TMP-SMX prophylaxis is still recommended for PJP in high-risk non-HIV patients in China.
肺孢子菌肺炎(PJP)在非HIV患者中显示出较高的死亡率。然而,这些患者中与耐药相关基因突变的数据有限。本研究旨在描述中国非HIV患者中二氢叶酸还原酶(DHFR)和二氢蝶酸合酶(DHPS)基因的突变流行情况,为药物使用提供参考。
我们分析了中国45例非HIV患者的DHPS和DHFR基因多态性,包括感染(n = 14)和定植(n = 31)。该分析还考虑了临床特征、负担、治疗反应和预后。
与定植相比,感染患者的血液指标(GR%、LY%、HGB、TP、ALB、CRP,P<0.05)有显著改变,负担更高(P<0.05),预后更差(P<0.05)。此外,感染患者更容易感染,如爱泼斯坦-巴尔病毒、巨细胞病毒、支原体和肺炎克雷伯菌。虽然本研究在DHPS基因中未检测到已知的耐药突变,但鉴定出10个非同义突变。此外,在DHFR基因中发现了10个非同义突变和2个同义突变。然而,这些突变与较差的预后无关。
我们的结果表明,在中国高危非HIV患者中,仍建议对PJP进行复方新诺明预防。